Selective cyclooxygenase-2 inhibitors and breast cancer

Fereshteh Moheb afzali,1,* Amir hendiani ,2

1. Department of Molecular and Cellular Biology , Faculty of Advanced Science and Technology , Tehran Medical Sciences , Islamic Azad University , Tehran , Iran .
2. Anesthesiologist , critical Care , Pain management Specialist , Iran University of Medical Sciences(IUMS) , Tehran , Iran .

Abstract

Introduction

Increasing the expression of biosynthesis of cyclooxygenase-2 (cox-2) and the production of prostaglandin e2 by adipocytes can stimulate estrogen receptors and induce cyp-1b1 in epithelial cells through the transcription of the cyp-19 gene and the biosynthesis of estrogens catalyzed by aromatase ; then estrogen hydroxylation and the production of estrogen quinones promote cell proliferation and lead to carcinogenesis of the breast. in the process of inflammation, prostaglandins produce peripheral sensory nerves and increase the sensitivity to pain of hyperalgesia. this phenomenon, along with inflammatory cytokines such as il-1, il-8 and tnf-α, is most likely to play an important role in stimulating cox-2 in the treatment of pain in the spinal cord. therefore, the objective of this study is to block the cox-2, which has the potential and potential for the prevention and treatment of breast cancer. the selective inhibitor of celecoxib, as a specific agent, can reduce tumor growth by at least 70% by blocking the production of angiogenic prostaglandin when treated at or before the tumor reaches a volume of 0.3 ml. multiple drug chemotherapy studies with celecoxib have shown that celecoxib reduces the threshold for allergy to chemotherapy. dependent doses of celecoxib control the effect of radiation therapy to reduce tumor volume and control tumor growth by reducing levels of peg2 from cox-2, which is caused by tumor stroma and, in some cases, tumor cells.

Methods

Based on the epidemiologic evidence that nonselective nsaids reduce human breast cancer risk, a case control study was started for selective cyclooxygenase-2 inhibitors to evaluate its effects on the relative risk of breast cancer.the study was conducted for women diagnosed with breast cancer patients were ascertained from the james cancer hospital, columbus, ohio, during the window of time (1998-2004) in which two selective cox-2 inhibitors, celecoxib and rofecoxib, were available by prescription in the united states. in the study, 323 cases with pathologically confirmed invasive breast cancer were compared to 649 controls without cancer who were frequency-matched at a 2:1 rate to the cases by age and county of residence. data on the past and current use of prescription and over the counter medications and breast cancer risk factors were ascertained using a standardized risk factor questionnaire. effects of cox-2 inhibiting agents were quantified by calculating odds ratios (or) and 95% confidence intervals.

Results

Results showed significant risk reductions for selective cox-2 inhibitors as a group (or = 0.29, 95% ci = 0.14–0.59), coxib use reduced the risk of breast cancer development by 71% (or = 0.29, p < 0.01). significant reductions in breast cancer risk were also noted for ibuprofen (63%) and regular 325 mg aspirin (49%) but not for low dose(81 mg) aspirin (23%). there was no effect of acetaminophen, an analgesic without cox-2 inhibiting properties(or = 1.02). the inverse pattern of risk for acetaminophen, low dose aspirin, regular aspirin, ibuprofen and coxibs was significant by a linear trend test (p < 0.05) suggesting that chemopreventive effects become progressively stronger with greater selective cox-2 inhibition.

Conclusion

This study showed a significant reduction in the risk of human breast cancer due to the use of selective cox_2 inhibitors. chemopreventive effects against breast cancer were associated with recommended daily doses of celecoxib(median dose = 200 mg) or rofecoxib (median dose = 25 mg) for an average duration of 3.6 years. notably,selective cox-2 inhibitors (celecoxib and rofecoxib) were only recently approved for use in 1999, and rofecoxib (vioxx) was withdrawn from the marketplace in 2004. nevertheless, even in the short window of exposure to these compounds, the selective cox-2 inhibitors produced a significant (71%) reduction in the risk of breast cancer, underscoring their strong potential for breast cancer chemoprevention.celecoxib has an effective role in the control of pain associated with inflammatory and cancerous causes due to selective cox_2 enzyme inhibition. in addition, significant therapeutic effects with fewer doses of administration make patients more comfortable with the drug. accordingly, if used on a regular basis, they can reduce the risk of human breast cancer.

Keywords

Breast cancer , cyclooxygenase -2, selective inhibitors , celecoxib